Marsh Classification Research Articles

Plasma Inflammatory Cytokines as Predictor Markers for Severity of Histological Variations of Intestine among Celiac Patients

Background: Celiac is a chronic hereditary intestinal disorder caused by autoimmune stimulation and injury of intestinal mucosa and different studies have reported an increase of inflammatory cytokines production in these patients. This study aimed to investigate the serum level of inflammatory cytokines and their correlations with the severity of histological variations among celiac patients. Material and methods: By a cross sectional study all celiac patients attending to gastrointestinal clinics in Ilam city during Oct. 2011- MAR. 2013 were investigated. Demographic data was collected using a validate questionnaire and patient's interview and each patient was taken a blood sample for laboratory investigation of tTG-IgA antibody via ELISA test and the serum level of hs- CRP, IL-6 and TNF-a was measured. All patients underwent endoscopic evaluation and biopsy samples were evaluated according to Marsh classification and correlation between severity of histological variations and serum levels of inflammatory cytokines was measured. Results: Totally 274 patients including 90 male and 184 female with a mean age of 28.8±14.4 years were evaluated. The mean serum levels of hs-CRP, IL-6 and TNF-a were 7.8±3.1 mg/l, 2.6±0.9 pg/ml and 6.9±4.6 pg/ml respectively (p=0.599, p=0.629 and p= 0.651). Hs-CRP showed a significant relationship with the severity of mucosal damage upon class I of Marsh classification (p=0.01); however, IL-6 showed a significant level among patients with Marsh I, II and IIIC (p=0.000, p=0.02 and p=0.000) but not in those with Marsh class IIIA and IIIB. Conclusion: There was a positive relationship between mean serum levels of IL-6 and TNF-a with increasing the Marsh classification from class I to class IIIC and the highest rate of IL-6 and TNF-a was shown in Marsh IIIC but the serum level of hs-CRP was not increased with Marsh class increasing. It was concluded that as the Marsh classification increased from class I to class IIIC, and/or the severity of pathologic variations was increased, the mean serum levels of inflammatory markers were increased too.

Intraepithelial Lymphocyte Normal Cut-off Level in Celiac Disease: The Debate Continues

The gold standard for diagnosis of celiac disease is positive serology confirmed by histological evidence of small intestinal biopsy damage as determined by the modified Marsh classification. Intraepithelial lymphocyte count has a pivotal importance in this grading criteria and the normal cut-off density has paramount importance in distinguishing between celiac disease and normal or false+ conditions. However its determination is problematic, complicated and far from being standardized. The localization along the villi or along the small bowel, the section thickness, the mode of detection and analysis, geoepidemiological influences, age dependency, associated infections or diseases and the strictness of the inclusions/exclusion criteria of the normal control group, all affect IEL density and normal cut-off levels. It is hoped that after standardization, the cut-off levels of IELs will better reflect the in-vivo reality to distinguish celiac disease from normal and associated conditions that affect intestinal IEL count.

Validity of Intraepithelial Lymphocyte Count in the Diagnosis of Celiac Disease: A Histopathological Study

The gold standard for diagnosis of Celiac disease (CD) is histological evidence of a small intestinal biopsy together with positive serology. Modified Marsh classification utilizes the histological parameter of intraepithelial lymphocyte (IEL) count in the diagnosis of CD. The reported upper limit of normal IEL in the duodenum varies from 20-40 per 100 epithelial cells (EC). The objectives of the study are to determine the normal upper limit of IEL in the duodenum and assess the diagnostic accuracy of existing criteria of IEL counts to diagnose CD. A retrospective analysis of histopathological records of duodenal biopsies reported as normal (control group, n=38) and consistent with CD (n=37) formed the basis of the study. IEL were counted in an uninterrupted length of surface epithelium and villous tips from formalin fixed, paraffin embedded, Haematoxylin and Eosin stained biopsies under the light microscope (X400 magnification). In the control group the mean IEL/100EC was 3.81(upper limit of normal = 7.78) and the mean IEL/villous tip was 0.96 (upper limit of normal = 3.5). In CD the mean IEL/100EC and mean IEL/villous tip were 20.93 and 6.83 respectively. The upper limit of normal IEL/100EC, mean IEL/100EC in CD and the villous tip IEL count in both the control and CD groups were considerably lower than those reported in other studies. The ethnicity, country of origin and environmental factors may be partly responsible for this observation. If high cut off values of IEL/100EC is taken to diagnose CD many cases may be under diagnosed, particularly when the upper limit of the normal IEL count is lower for that population and region, highlighting the importance of a multidisciplinary approach in the diagnosis of CD.

Coeliac disease: to classify or not to classify - that is the question!

Coeliac disease: to classify or not to classify - that is the question!

Percentage of Patient with Celiac Disease among Children with Short Stature

Background: Clinical features of celiac disease vary considerably. Intestinal symptoms are common in children whose disease is diagnosed within the 1st 2 years of life. As the age at presentation of the disease shifts to later in childhood, and with the more liberal use of serologic screening tests, extra-intestinal manifestations and associated disorders, without any accompanying digestive symptoms, have increasingly become recognized, including short stature. We aim in this study to determine the percentage of celiac disease among patients with short stature. Objectives of the Study: (1) to show the percentage of patient with celiac disease in short stature children. (2) to show the effect celiac disease on treatment of short stature children. Methodology: A cross sectional study that carried out at the Endocrine Pediatrics Clinic at A Zahraa Teaching Hospital for a period in 1st of January 2013 to end of October 2013; a total of 167 children and adolescents, aged range of 2 to 18 years were registered with short stature . 91 children of them only have been enrolled in this study according to inclusion criteria. Enzyme immunoassay (Biosystems, Spain) was used to determine IgA tTG using microplate tests. Samples with concentrations >20U/mL were defined as positive. Patients with positive anti-tTGserology were referred to the gastroenterology clinic to continue investigation of celiac disease by endoscopy and biopsy. Data were analyzed by SPSS software in IBM version 20 using chi square and paired T-test. Result: A total of 167 patients were evaluated 91 of them only have been enrolled in our study according to inclusion criteria; 59 (65%) were female and 32 (35%) were male. Median age was 9 years (of 2 - 18 years).The anti-tTG assays were positive in 16.5% of patients (15/91). Out of 15 patient whose diagnosed as anti-tTG positive, 11 (73%) have been diagnosed as celiac disease by endoscopy and biopsy according to modified marsh classification. All children diagnosed to have celiac disease were kept on a gluten-free diet. Patients were followed-up for six months and showed improvement in growth rate. Conclusion: Celiac disease a cause of short stature that should be included in diagnostic investigations of short stature.Recommendation: anti-tTG antibody as routine test recommended for all patients with short statures. All patients with idiopathic short statures and anti-tTG test positive with normal IgA level should be subjected to intestinal biopsy to prove the diagnosis of celiac disease.

Prevalence of Celiac Disease in Children With Iron Deficiency Anemia in Van Lake Region of Turkey.

We aimed to determine the prevalence of celiac disease (CD) in children with iron deficiency anemia (IDA) and compare the hematological variables of these children with those with IDA, but not with CD. A total of 250 patients aged 1 to 16 years with IDA were included. Upper gastrointestinal system endoscopy was recommended to the patients who were serologically positive for CD. According to the endoscopic biopsy results of 12 patients who have positive screening tests (57.1%), Marsh grade II histopathologic findings were detected in 1 (4.8%) and Marsh grade III histopathologic findings were detected in 11 (52%). The hemoglobin, hematocrit, iron, and ferritin levels were significantly lower in patients with CD with IDA, compared with those with IDA, but not with CD. According to Marsh classification, the percentage of Marsh grade IIIc was found to be higher than the other Marsh grades. As the Marsh grading increased, hemoglobin, hematocrit, serum iron, and ferritin levels decreased and tissue transglutaminase Ig A levels increased. Our results show that CD should be kept in mind as the underlying etiologic factor in patients with IDA.

Letter to the Editor GHFBB; Response to Peña AS: What is the best histopathological classification for celiac disease? Does it matter?

To The Editor: The editorial by Pena AS: (1) and the responses elicited by it are of major importance. Everyone concur that patient’s wellbeing; proper diagnosis and treatment are the main objective. Let’s not forget that these concepts and guidelines are used by those rendering the direct health service to the public, by policy makers and regulators, which often need to relay on the opinion of experts on the field. Hence, communication and transfer of information needs to be clear, and applicable to patient care and public health. Evaluation of new therapeutic products to manage celiac disease (CD), requires agreement on guidelines for diagnosis (Dx) and follow up, including: diagnostic methods, reproducibility, validation and sensitivity. Standardization of best practice guideline may improve detection of CD in regions with limited human resources and equipment. Recruiting of CD patients for clinical trials is usually challenging, particularly because the need of biopsy as part of the Dx. The lack of animal models to assess new therapeutic compounds enhances the need to use clinical trials at earlier stages of drug development, adding a challenge and need for standardization of Dx guidelines. With these in mind: I agree that in cases of suspected CD and conditions linked to adverse reactions to gluten, small bowel biopsy procedures, including: sampling, processing, evaluation tools, classification and interpretation are key for differential diagnosis and management. The need of standardizing histopathology classification that can be used worldwide is essential. Pena AS (1), provide a very useful tabulated comparison among different classifications, facilitating the interpretation of publications using various classifications, allowing for compilation and analysis of data for public health. The idea of re-assessing the emphasis on the biopsy as a gold standard in the diagnosis of CD, in light of available less invasive tests, is a welcoming one, at least reducing the number of biopsies required for follow up. Villanacci (2) emphasizes on reproducibility and the use of simpler classification to facilitate reproducibility, but his suggested classification seems over simplified. Clinicians shall decide if that will be sufficient for proper Dx and management. Villanacci (2, 3) points out the advantage of including the term of “Microscopic Enteritis” (4) as a separate histopathology Dx, a practical suggestion for differential diagnosis. Marsh, Villanacci and, Srivastava (5) illustrate the differences between the histopathology of CD Marsh classification (4), and non-celiac gluten sensitivity. Despite its limited explanation, this publication is very useful to pathologists. Could this classification be modified not to use morphometric analysis? Do the Villanaci (2, 3) simplified classification provide the information required for best practice? These questions need consensual response for best practice guidelines worldwide. Nonetheless and until proven otherwise evaluation of new therapeutic products are best to use the Marsh classification (5). It calls my attention that in this discussion there is no mention of differences in diagnostic approach between pediatric and adult cases, since the need for the use of biopsy in pediatric has been questioned. Do you have any thoughts on that? The concern expressed by Walker (6) is a valid one, but if anything is complementary to Pena AS (1) editorial. International guidelines cited are the key to standardization on diagnosis and management of CD, and gluten free-diet (GFD) as the therapy of choice, which carries an emotional, and financial impact. The ACG Clinical Guidelines: Diagnosis and Management of CD published by Rubio-Tapia et al. (6) indicates that a diagnosis of CD requires the demonstration of histological changes associated with the disease, classified according to: Marsh, Marsh modified (Oberhuber), or by the more recent, simplified Corazza classification. It accepts the incorporation of simplified classifications for the general practice.

Prevalence of Celiac Disease in Children With Type 1 Diabetes Mellitus in Southeast Region of Turkey

Background: Although the relationship between celiac disease (CD) and type 1 diabetes mellitus (DM) is well recognized, there are no studies of this association in Southeast Region of our country. The aim of this study was to identify the prevalence of CD in a group of children with type 1 DM undergoing treatment in the Pediatric Endocrinology Department of our hospital. Methods: The patients followed up with diagnosis of type 1 DM in the Outpatient Clinics of Pediatric Endocrinology in our hospital were enrolled in the study. Anti-tissue transglutaminase (anti-tTG) IgA was measured in blood collected from these patients. Patients with anti-tTG IgA positive then had duodenal biopsy. Biopsy samples were obtained through an endoscopy procedure. Biopsy specimens were evaluated and classified according to Marsh classification. Results: The study participants consisted of 218 patients (girls, n = 117: 53.7%; boys, n = 101: 46.3%) with type 1 DM with a mean age of 12.9 ± 4.5 years (range 2 - 18 years). Sixteen patients had anti-tTG IgA positive. All of the cases with positive serology underwent duodenal biopsy. On histopathological evaluation, 11 patients had mucosal alterations compatible with celiac disease; five patients had non-specific histologic changes or normal biopsies. The prevalence of CD was 5% among 218 patients. Five cases with normal biopsy results were evaluated as having latent CD. Conclusions: These findings indicate that the prevalence of CD in children with type 1 DM was higher than that in general population. Periodic screening of diabetic children and adolescents in terms of CD is indicated to ensure early diagnosis and treatment. Int J Clin Pediatr. 2016;5(2):32-35 doi: http://dx.doi.org/10.14740/ijcp239w

Cardiac functions assessment in children with celiac disease and its correlation with the degree of mucosal injury: Doppler tissue imaging study

Background/Aims:Celiac disease (CD)-associated cardiologic disorders is a growing concern. However, data regarding cardiac affection in children with CD are few. This study aimed at assessing the subclinical impact of CD on the global myocardial performance in Saudi children with CD using Doppler tissue imaging (DTI).Patients and Methods:Conventional two-dimensional echocardiography was performed among 20 Saudi children with CDas well as 20 age and sex-matched healthy controls. DTI were used to determine right ventricular (RV) and left ventricular (LV) Tei indexes. These findings were correlated with the Modified Marsh Classification of the histologic findings in CD.Results:LV and RV Tei indexes were significantly higher in children with CD than the control group (mean ± standard deviation: 0.47 ± 0.05 vs. 0.31 ± 0.18; P < 0.0005 and 0.51 ± 0.04 vs. 0.32 ± 0.05; P < 0.0001, respectively). RV Tei index was found to be positively correlated with the Modified Marsh Classification of CD (r = 0.7753, P < 0.0001). LV Tei index tended to be more affected in patients with more severe histologic findings, however, such relation did not reach statistical significance (r = 0.2479, P = 0.292). Fractional shortening did not correlate with the Modified Marsh Classification of histologic findings in CD patients (r= −0.11, P = 0.641).Conclusions:Subclinical myocardial dysfunction of both ventricles occurs in children with CD. The DTI method appears to be more sensitive than conventional two-dimensional echocardiography in the early detection of myocardial dysfunction in children with CD.

What is the best histopathological classification for celiac disease? Does it matter?

What is the best histopathological classification for celiac disease? Does it matter?

Oberhuber versus Marsh: much ado about nothing?

This issue of the journal features a spirited debate between Oberhuber and Marsh et al regarding the existence and significance of Oberhuber’s sub-classification of the Marsh III lesion into III a, b, c categories. The controversy stems from an article by Marsh and colleagues in an earlier issue of this journal where they present scanning electron microscopic (SEM) images from two cases classified as IIIc to suggest that these lesions consist of multiple crypts opening into large basins that are surrounded by concentric arrays of enterocytes. Their main contention was that Oberhuber’s category IIIa and IIIb lesions do not exist since no “atrophic” or “partially degenerate” villi were seen on the SEM examination. As Oberhuber points out in his response, included in this issue, the contention of Marsh and colleagues is supported mainly by the SEM images from two cases that were both IIIc lesions. It is certainly true that the prior study by Marsh and colleagues would have been strengthened immensely had they included a larger series of biopsies with variable degrees of villous atrophy from a well-characterized cohort of patients with celiac disease. One cannot argue with certainty regarding the absence of a particular feature or category by examining a small number of cases, no matter how sensitive the technique utilized by the observer. The debate regarding the question of Marsh category I or II lesions evolving directly into completely flat mucosa, as proposed by Marsh et al, or evolving through intermediate stages with partially degenerate villi that can be reproducibly recognized as Oberhuber’s categories IIIa or IIIb is likely to continue in the near future until a systematic large series of biopsies is examined both by routine histology and SEM examination. The Marsh classification (1) was a major paradigm shift that moved us away from the idea of some magical threshold of intraepithelial lymphocytes (IELs) or villous abnormalities that could help us confidently diagnose or rule out celiac disease. Instead, it highlighted the range of morphological possibilities that exist within patients with celiac disease. Oberhuber’s effort at

Reply to: Mucosal histopathology in celiac disease: a rebuttal of Oberhuber´s subdivision of Marsh III.

To The Editor: We read with interest the paper entitled “Mucosal histopathology in celiac disease: a rebuttal of Oberhuber´s sub-division of Marsh III” by MN Marsh et al. published in this Journal (1). We have proposed a standardized classification system of the celiac lesions in 1999 (2).In their paper Marsh et al. comment on this work. To our surprise, the authors of the paper suggest that the flat mucosa (type IIIc in the modified Marsh classification) is the only acceptable and a provable stage of the destructive type of a CD lesion. According to their opinion, stages IIIa and b do not exist. They support their notion by comparing the scanning electron microscopy (SEM) of two IIIc lesions in fig. 2 and 3 accompanied by the corresponding conventional histological picture. In fig. 3 they demonstrate a section that could be mistaken for a “villous” projection as depicted in their figure legend. In our opinion only an inexperienced histopathologist would classify this lesion as IIIb. In fig. 6 they furthermore demonstrate that the severity of mucosal atrophy could be underestimated in histological sections passing through a collared basin. Unfortunately they only presented a cartoon to elucidate this type of error. We doubt that they are able to demonstrate such a lesion on histological sections. Furthermore, they ignore the fact that the interpretation of histological lesions in biopsies is performed on serial sections. Serial sections help to avoid this type of error.. Marsh and his team did not demonstrate the SEM of a histological lesion that could be clearly classified as type IIIa or b in the conventional histology. In our opinion such an attempt would have lead to a dismissal of their proposal. Furthermore, the authors were also prey to an error in their conception they suggest that an early lesion without villous flattening (type I or II lesion) turns into a flat mucosa without intermediary stages. Therefore, the villi would show a normal shape in the type I or II lesions, and then immediately become flat. We do not think that this is possible.

Validity of histology for the diagnosis of paediatric coeliac disease: a Swedish multicentre study

Objective Histological evaluation of intestinal biopsies for the diagnosis of coeliac disease can be challenging and compatible with risk of misdiagnosis. The aim was to evaluate the agreement of pathological diagnosis for coeliac disease in children investigated at four major paediatric university hospitals in Sweden. Materials and methods Intestinal duodenal biopsies were collected from 402 children at median 9.7 years (1.4–18.3 years). A pathologist at each hospital performed the primary evaluation. A designated pathologist, blinded to the primary evaluation, performed a second Marsh classification of biopsies (M0 to M3c) taken from the bulb and duodenum separately. Kappa (κ) scores between first and second evaluation determined the agreement. Plasma samples were collected at the day of intestinal biopsy and analysed for tissue transglutaminase autoantibodies (tTGA) using radioligand-binding assays. Results Marsh scores were concordant in 229/356 biopsies (64%, κ = 0.52, p < 0.0001). Among discordant results, 15/127 (12%) showed M0 in distal duodenum but ≥ M2 in the bulb, whereas the opposite was true for 8/127 (6%) of the biopsies. There were fewer collected duodenal biopsies, more missing bulb biopsies and missing CD3 staining among discordant evaluations. The second evaluation revealed a Marsh score compliant with coeliac disease in 22 children of whom seven children were tTGA positive. Conclusions The variation between university hospitals on the pathological evaluation of biopsies may lead to misdiagnosis of coeliac disease in paediatric patients. Access to clinical and endoscopic information as well as tTGA levels may be useful for the pathologist to complement the evaluation in dubious cases.

Prevalence of inflammatory bowel disease among coeliac disease patients in a Hungarian coeliac centre.

BackgroundCeliac disease, Crohn disease and ulcerative colitis are inflammatory disorders of the gastrointestinal tract with some common genetic, immunological and environmental factors involved in their pathogenesis. Several research shown that patients with celiac disease have increased risk of developing inflammatory bowel disease when compared with that of the general population. The aim of this study is to determine the prevalence of inflammatory bowel disease in our celiac patient cohort over a 15-year-long study period.MethodsTo diagnose celiac disease, serological tests were used, and duodenal biopsy samples were taken to determine the degree of mucosal injury. To set up the diagnosis of inflammatory bowel disease, clinical parameters, imaging techniques, colonoscopy histology were applied. DEXA for measuring bone mineral density was performed on every patient.ResultsIn our material, 8/245 (3,2 %) coeliac disease patients presented inflammatory bowel disease (four males, mean age 37, range 22–67), 6/8 Crohn’s disease, and 2/8 ulcerative colitis. In 7/8 patients the diagnosis of coeliac disease was made first and inflammatory bowel disease was identified during follow-up. The average time period during the set-up of the two diagnosis was 10,7 years. Coeliac disease serology was positive in all cases. The distribution of histology results according to Marsh classification: 1/8 M1, 2/8 M2, 3/8 M3a, 2/8 M3b. The distribution according to the Montreal classification: 4/6 Crohn’s disease patients are B1, 2/6 Crohn’s disease patients are B2, 2/2 ulcerative colitis patients are S2. Normal bone mineral density was detected in 2/8 case, osteopenia in 4/8 and osteoporosis in 2/8 patients.ConclusionsWithin our cohort of patients with coeliac disease, inflammatory bowel disease was significantly more common (3,2 %) than in the general population.

The DQ2 ALLELE, DQB1∗02:02, Differentiates mild from severe histology in adult celiac disease patients

Aim Celiac disease (CD) is a T cell, immune-mediated, small bowel disease caused by gluten exposure in patients with a genetic predisposition. It is highly associated with DQ2 and DQ8. Most CD patients type as either DQA1∗05:01/DQB1∗02:01,or DQA1∗03:01/DQB1∗03:02. A third group with DQ2 subtype DQA1∗02:01/DQB1∗02:02 was also noted. We examined the clinical characteristics of four groups of CD patients, including those positive for both DQ2 and DQ8. Methods Tissue typing was performed with LabType class II kits (One Lambda ThermoFisher,Canoga Park CA). SSP was performed to confirm alleles. Patient data was derived from a retrospective, cross sectional chart review. The Marsh Classification was used to characterize patients according to histological findings including degree of villous blunting, intraepithelial lymphocytosis and lamina propria expansion. Marsh Scoring ranges from M0 (normal) to M4 (total villus blunting). Results Of 89 adult patients with biopsy-proven CD, 45 ( 51%) carried the expected HLA DQA1∗05:01/DQB1:02:01(DQ2); 15 (16%) had DQA1∗03:01/DQB1∗03:02(DQ8), 7 (8%) had DQB1∗03:02 plus DQB1∗02:01(DQ8 + DQ2) together, and 22(25%) typed as DQA1∗02:01/DQB1∗02:02(DQ2). The M0 and M1 combined score was found in 64% of the DQB1∗02:02 group compared with 31% in the DQB1∗02:01 group (OR = 0.26, P = .017). Conclusions Patients with DQB1∗02:02 are four times more likely to have Marsh Scores of 0-1, than patients with DQB1∗02:01. These less severe histologic changes may be associated with a better prognosis. Our study reports a 24% prevalence of the allele DQB1∗02:02 compared with previous reports of 4% in adults. Download : Download full-size image

Exocrine pancreatic insufficiency, MRI of the pancreas and serum nutritional markers in patients with coeliac disease

ObjectivesTo determine whether exocrine pancreatic function is impaired in patients with coeliac disease (CD) in our population and to evaluate its clinical importance.MethodsPancreatic exocrine function was determined by measuring faecal...

The degree of mucosal damage to the small intestine and serum immunoglobulin G4 levels correlate with celiac disease.

Celiac disease (CD) is an immune-mediated and chronic inflammatory enteropathy, triggered by the ingestion of gluten in genetically susceptible individuals. Immunoglobulin G4 (IgG4)-related diseases are a recently defined emerging clinical condition, characterized by increased serum IgG4 concentrations. The aim of this study was to investigate whether IgG4 levels correlate with the titers of intestinal antibodies and the degree of mucosal damage in CD patients. A total of 41 CD patients and 28 healthy controls were included in the study. All patients underwent a duodenal biopsy and were then diagnosed with the modified Marsh classification. Blood samples were obtained for IgG4 measurements. Serums were kept at -80 °C until the analysis was carried out and plasma IgG4 levels were determined using an enzyme-linked immune sorbent assay method with a diagnostic cutoff value of 135 mg/dl. The mean age of the CD and the control group was 26.8 ± 8.3 and 26.9 ± 6.2 years, respectively. The mean IgG4 levels were significantly higher in CD patients (283.21 ± 39.02 mg/dl) compared with the healthy control group (68.97 ± 15.89 mg/dl, P<0.0001). In the CD group, 27/41 patients and in the control group, 4/28 patients had high IgG4 levels (>135 mg/dl, P < 0.0001). A close correlation was found between the grade of mucosal damage, IgG4 levels, and antigliadin-IgA; the higher the grade Marsh score, the higher the measured IgG4 (P < 0.05). In our study, IgG4 levels of CD patients were higher than normal ranges whereas the results of the control group were within physiologic limits. We also showed for the first time that there was a correlation between IgG4 levels, autoantibody, and severity of mucosal damage. To the best of our knowledge, this is the first study to evaluate IgG4 levels and mucosal damage in CD patients.

Prevalence of celiac disease in adult patients with iron-deficiency anemia of obscure origin in Kashmir (India).

The purpose of this study was to evaluate the prevalence of celiac disease in adult patients with iron-deficiency anemia of obscure origin. One hundred and sixty-one consecutive patients with iron-deficiency anemia of obscure origin were evaluated. Tissue transglutaminase antibodies levels were done and duodenal biopsies were scored according to Marsh classification. Diagnosis was based on positiveIgA anti-tissue transglutaminase antibodies and abnormal histopathology. Gluten-free diet (GFD) was adviced for celiac disease patients. One hundred and sixty healthy blood donors were tested for IgA anti-tissue transglutaminase antibodies, and positive controls were subjected to endoscopic duodenal biopsy. Tissue transglutaminase antibodies were positive in 13 (8%) patients with iron-deficiency anemia of obscure origin and 4 (2.5%) in control group (p = 0.026) (odds ratio 3.42; 95% confidence interval [CI]: 1.092-10.743). All 13 patients (8%) and 2 out of 4 positive controls (1.25%) had histopathology findings of celiac disease (p = 0.004). Duodenal biopsy showed Marsh grade 1 in 4, grade 2 in 4 (30.77%), 3a in 1 (7.70%), 3b in 2 (15.38%), and 3c in 2 (15.38%) patients. A statistically significant correlation was found between lower hemoglobin concentration and higher Marsh grading (Spearman's rho = -0.946, p = 0.001). Celiac disease patients adhered to GFD and after 6months mean (SD) hemoglobin levels increased from 7.42 ± 0.96 to 10.47 ± 0.80g/dL (p- < 0.001). Patients with iron-deficiency anemia of obscure origin had increased prevalence of celiac disease. Gluten-free diet improved anemia in celiac disease patients irrespective of grade of duodenal involvement.

PTU-161 An opportunity missed in diagnosing coeliac disease: Abstract PTU-161 Table 1

Introduction The prevalence of coeliac disease (CD) is around 1% in the UK. The ‘gold standard’ diagnosis of CD requires a distal duodenal (D2) biopsy when the patient is on a gluten containing diet and in most cases positive serology (eg tissue transglutaminase antibodies, tTG ab). CD is confirmed when histological criteria as set out in the Marsh classification [increased intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy (VA)] are met. The diagnosis of CD may be delayed as it can present with a wide range of signs and symptoms including iron deficiency anaemia, weight loss, osteoporosis, neuropathy and vague abdominal symptoms. Many patients with vague abdominal symptoms undergo upper GI endoscopy (OGD), however, in the majority D2 biopsies to look for CD are not obtained. Endoscopic examination may reveal classical features of VA such as ‘scalloping’ of the duodenal mucosa but may also be normal. The aim of the study was to evaluate the range of duodenal endoscopic findings in patients with proven CD and VA on D2 biopsy. Method A single centre, retrospective analysis of patients with histologically proven CD (Marsh 3 classification) on D2 biopsies in a London district general hospital was performed. Data was obtained from the hospital’s histology database, endoscopy reporting software and electronic patient record system. Information on the patients’ demographics, symptoms, index endoscopy findings, histology and coeliac serology prior to a gluten free diet was scrutinised. Results 65 patients had a confirmed diagnosis of CD with VA. 6 patients were excluded from our analysis as endoscopy reports were unavailable. Of the remaining 59, there were 36 females and 29 males. Indications for endoscopy based on patients presenting symptoms were as follows: 18/59 for iron deficiency anaemia, 12/59 (abdominal pain/bloating), 11/59 (diarrhoea), 10/59 (asymptomatic but positive tTG ab), 6/59 (weight loss) and 2/59 for fatigue. tTG ab was positive in 50/59 patients, negative in 7 and not tested in 2. The Table 1below shows the endoscopy findings in these 59 patients with CD. Conclusion Over half of our CD patient cohort had normal endoscopic findings on diagnosis despite confirmed VA on D2 biopsies. 17% of patients were asymptomatic at diagnosis and 12% of patients were tTG ab negative. Given the wide ranging clinical presentation of CD and its overall prevalence, D2 biopsies should not be limited to patients presenting with classical symptoms as we may be missing the opportunity to diagnose this easily treatable condition. We recommend that all patients presenting to OGD for vague abdominal symptoms have duodenal biopsies to exclude CD. Disclosure of interest None Declared.

PTU-160 Raised intraepithelial lymphocytes in the presence of normal small bowel mucosa: confirmation of coeliac disease in clinical practice

<h3>Introduction</h3> Raised intraepithelial lymphocytes (IEL) (&gt;30–40 IEL/100 enterocytes) in small bowel (SB) mucosa is associated with coeliac disease (CD) when accompanied by distorted villous architecture. In addition to CD, there are other causes of raised IEL including NSAIDs, autoimmune conditions, tropical sprue, H pylori associated gastritis and intestinal lymphoma. It is recommended that patients who have raised IEL without distorted villous architecture (Marsh classification Stage 1 criteria) undergo further serological testing along with HLA DQ2 DQ8 genotyping to assist in the diagnosis of CD. The aim of the study was to determine the further assessment in clinical practice of patients with raised IELs in otherwise normal SB biopsies to confirm the diagnosis of CD. <h3>Method</h3> A single centre, retrospective analysis of patients with the histological finding of raised IELs on distal duodenal (D2) biopsies in a district general hospital was performed. A database of patients with raised IEL was obtained from the hospital histology database and data on the patients coeliac antibody result, symptoms, diagnosis and management was scrutinised using the electronic patient record system. <h3>Results</h3> 121 patients had raised IEL on D2 biopsy specimens. 58 of these patients had a confirmed diagnosis of CD with villous atrophy. The remainder (63) had raised IEL with preserved villous architecture. 48/63 patients were negative for coeliac antibodies, 1 was positive and 14/63 (22.2%) were not tested. 15/63 (23.8%) were initiated on a gluten free diet and of this, 4 did not report an improvement in their symptoms despite adherence. Only 2 patients had HLA DQ2/DQ8 testing to aid in the diagnosis of CD. A final diagnosis of CD was made in 11/63 (17.5%) patients meeting Marsh 1 criteria. 32/63 (50.8%) patients had a diagnosis of gastrooesophageal reflux disease (GORD) including 10 patients (15.9%) with H pylori associated gastritis. H pylori was not tested in 13/32 patients with GORD (40.6%). A third of patients (20/63 = 31.7%) with raised IEL and normal SB mucosa did not undergo any further specific investigation to elucidate the cause of the raised IELs. <h3>Conclusion</h3> There is marked variability in management of patients following the findings of raised IEL with normal SB mucosa. A fifth of patients did not have coeliac antibody tested and only 2 patients had HLA DQ2 DQ8 genotype assessment. Latent CD was diagnosed in almost a fifth (17.5%) of patients with raised IEL and preserved villi whilst GORD and H pylori gastritis were present in half of the patients with this finding. We recommend that all patients in whom raised IELs are identified have coeliac serology and HLA DQ2 DQ8 testing to exclude CD prior to entertaining other diagnoses in clinical practice. <h3>Disclosure of interest</h3> None Declared.